PB2227: TRANSFORMATION OF MYELOPROLIFERATIVE NEOPLASMS INTO ACUTE PROMYELOCYTIC LEUKEMIA: SYSTEMATIC REVIEW AND META-ANALYSIS OF CASE REPORTS
Authors: Mihnea-Alexandru Găman
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: BCR-ABL1-negative classical myeloproliferative neoplasms (MPNs), i.e., polycythemia vera (PV), essential thrombocythemia (ET) and primary (PMF) or secondary myelofibrosis (SMF), exhibit a propensity towards the development of thrombotic complications, as well as a risk of transformation into acute myeloid leukemia (AML). However, transformation of MPNs into acute promyelocytic leukemia (APL), a distinct subtype of AML, has rarely been reported and data on its occurrence are scarce. Aims: Provide an overview of the cases of APL transformed from MPNs and report on epidemiology, clinical presentation, diagnostic tools, treatment and outcomes. Methods: Systematic search computed in PubMed/Medline from the inception of these databases until 01.03.2023, to identify relevant English-written articles. Eligibility criteria: 1. Confirmed MPNs diagnosis, 2. Confirmed diagnosis of APL, 3. Availability of full-texts and information on the selected outcomes. Results: The systematic search yielded 103 potentially relevant papers. After screening of abstracts/titles (n=91), 12 manuscripts were selected for full-text review. After applying the eligibility criteria, 11 articles were entered into the qualitative and quantitative analysis. In total, 11 case reports of MPNs transformed into APL were detected: 63.0% females, mean age at MPN diagnosis 53±7.4 years, range 38-66 years. Most reports (55.0%) came from Asia (5 from China, 1 from Japan) and were published between 1997 and 2023. In total, most cases of APL transformed from MPNs emerged from ET (4 cases, 37%) or post-ET SMF (2 cases, 18%), followed by PMF (3 cases, 27%) and PV (2 cases, 18%). JAK2V617F was detected in 55% of cases, CALR type 1 mutation in 1 case (10%), and genetic testing was unreported in the rest. Treatment for MPNs mostly consisted of hydroxyurea (HU; 7 cases, 64%), in association with phlebotomy and/or antiplatelet agents (aspirin). Mean time from MPN transformation into APL was of 4.4 + 6.5 years (range 0-22 years). In 3 cases, APL and MPNs were discovered simultaneously and the evolution of the MPN clone into APL was proven by molecular diagnostics (e.g. whole exome sequencing). APL presentation consisted mostly of general symptoms (fatigue, 27%; weight loss, 27%; fever, 18%), hemorrhagic syndrome manifestations, e.g., bleeding (45%) and/or pancytopenia (45%) on the complete blood count. Diagnosis of APL was confirmed in all cases by bone marrow assessment (aspirate/biopsy), cytogenetics/FISH with t(15;17) detection, molecular biology (RT-PCR for PML:RARA), and in some cases also by flow-cytometry. APL induction treatment consisted in all-trans retinoic acid (ATRA; 91%) in association with chemotherapy (anthracyclines, 64%) and/or arsenic trioxide (ATO, 55%). APL consolidation employed ATRA (36%), ATO (27%) and/or chemotherapy (55%) alone or in different combinations. Complete molecular remission was achieved in 9 cases (82%), unreported in 1 case, and 1 patient underwent allergenic stem cell transplantation but died due to CNS relapse. Summary of the reported cases in presented in the attached Table.Summary/Conclusion: Transformation of MPNs into APL is rare occurrence, yet must be taken into consideration particularly in patients of Asian ethnicity diagnosed with ET, JAK2V617F-positive MPNs, MPNs who were treated with HU and/or who present with hemorrhagic manifestations and/or pancytopenia. However, current data suggests that complete molecular remission can be achieved in most to all cases of APL transformed from MPNs with ATRA and/or chemotherapy-based regimens. Keywords: Thrombocythemia, Acute promyelocytic leukemia, Myeloproliferative disorder, Idiopathic myelofibrosis